Association of Inflammatory markers with pregnancy loss: Global Burden (1990-2021) and NHANES survey (2005-2016)

This study systematically characterized the global burden of pregnancy loss from 1990 to 2021 and evaluated the association between inflammatory markers and pregnancy loss, aiming to reduce the risk of pregnancy loss.

A comprehensive analysis was conducted, encompassing the incidence, deaths, disability-adjusted life years (DALYs), and years lived with disability (YLDs), across a total of 204 countries. This analysis was complemented by the implementation of joinpoint regression and ARIMA models, which were utilized to assess trends and projections. Additionally, inflammatory markers were analyzed in a cohort of 5,517 U.S. women. The association between inflammatory markers and pregnancy loss was assessed using survey-weighted multivariate logistic regression. Subsequently, restricted cubic spline (RCS) plots were utilized to explore the non-linear association between inflammatory markers and pregnancy loss. Subgroup analyses were conducted to further elucidate the effects of other covariates on the association between inflammatory markers and pregnancy loss.

Globally, the incidence of pregnancy loss has been observed to decline at a rate of 1.5% per annum, with a concomitant decrease in mortality of 64.8% from 1990 to 2021. The regions exhibiting the highest-burden were those with a low socio-demographic index (SDI), with an average age-standardized incidence rate (ASIR) of 1,715.1 per 100,000. In contrast, High SDI regions demonstrated rates below 500 per 100,000. Projections indicate a continued global decline to 725.2 cases/100,000 by 2032, though High SDI regions may face rising rates (3.66% annually). A U-shaped association between neutrophil-to-lymphocyte ratio (NLR) and miscarriage risk was revealed by NHANES analysis, with moderate NLR levels (the third quartile-the fourth quartile) linked to reduced odds (OR: 0.75-0.76, p < 0.05). Subgroup analyses revealed stronger associations in women aged ≤ 35 years and those with a Body Mass Index (BMI) of 25-30 kg/m².

These findings challenge the notion of linear inflammatory risk, emphasizing immune homeostasis's role in pregnancy maintenance. The study underscores persistent disparities in low-resource settings and advocates for integrating inflammatory markers into clinical risk stratification. Public health strategies must address inequities through targeted antenatal care, while high-income regions require interventions targeting delayed childbearing and metabolic health. This dual approach may mitigate the evolving global burden of pregnancy loss.